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General Information About Esophageal Cancer

Two histologic types account for the majority of malignant esophageal neoplasms: adenocarcinoma and squamous cell carcinoma. Adenocarcinomas typically start in the lower esophagus and squamous cell carcinoma can develop throughout the esophagus. The epidemiology of these types varies markedly.

Incidence and Mortality

Estimated new cases and deaths from esophageal cancer in the United States in 2018:[1]

New cases: 17,290.

Deaths: 15,850.

The incidence of esophageal cancer has risen in recent decades, coinciding with a shift in histologic type and primary tumor location. In the United States, squamous cell carcinoma has historically been more prevalent although the incidence of adenocarcinoma has risen dramatically in the last few decades in the United States and western Europe.[2,3] Worldwide, squamous cell carcinoma remains the predominant histology, however, adenocarcinoma of the esophagus is now more prevalent than squamous cell carcinoma in the United States and western Europe.[4] The incidence of adenocarcinoma has increased most notably among white males.[5] In the United States, the median age of patients who present with esophageal cancer is 67 years.[6] The majority of adenocarcinomas are located in the distal esophagus. The cause for the rising incidence and demographic alterations is unknown.

Anatomy

The esophagus and stomach are part of the upper gastrointestinal (digestive) system.

The esophagus serves as a conduit to the gastrointestinal tract for food. The esophagus extends from the larynx to the stomach and lies in the posterior mediastinum within the thorax in close proximity to the lung pleura, peritoneum, pericardium, and diaphragm. As it travels into the abdominal cavity, the esophagus makes an abrupt turn and enters the stomach. The esophagus is the most muscular segment of the gastrointestinal system and is composed of inner circular and outer longitudinal muscle layers. The upper and lower esophagus are controlled by the sphincter function of the cricopharyngeus muscle and gastroesophageal sphincter, respectively. The esophagus has a rich network of lymphatic channels concentrated in the lamina propria and submucosa, which drains longitudinally along the submucosa.

Tumors of the esophagus are conventionally described in terms of distance of the upper border of the tumor to the incisors. When measured from the incisors via endoscopy, the esophagus extends approximately 30 to 40 cm. The esophagus is divided into four main segments:

Risk factors associated with esophageal adenocarcinoma are less clear.[3] Barrett esophagus is an exception and its presence is associated with an increased risk of developing adenocarcinoma of the esophagus. Chronic reflux is considered the predominant cause of Barrett metaplasia. The results of a population-based, case-controlled study from Sweden strongly suggest that symptomatic gastroesophageal reflux is a risk factor for esophageal adenocarcinoma. The frequency, severity, and duration of reflux symptoms were positively correlated with increased risk of esophageal adenocarcinoma.[7]

(Refer to the PDQ summary on Esophageal Cancer Prevention for more information.)

Prognostic Factors

Favorable prognostic factors include the following:

Early-stage disease.

Complete resection.

Patients with severe dysplasia in distal esophageal Barrett mucosa often have in situ or invasive cancer within the dysplastic area. After resection, these patients usually have excellent prognoses.[8]

In most cases, esophageal cancer is a treatable disease, but it is rarely curable. The overall 5-year survival rate in patients amenable to definitive treatment ranges from 5% to 30%. The occasional patient with very early disease has a better chance of survival.

Related Summaries

Other PDQ summaries containing information related to esophageal cancer include the following:

Esophageal Cancer Prevention

Esophageal Cancer Screening

Unusual Cancers of Childhood Treatment

For information about gastrointestinal stromal tumors, which can occur in the esophagus and are usually benign, refer to the following summary:

Gastrointestinal Stromal Tumors Treatment

For information about supportive care for patients with esophageal cancer, refer to the following summaries:

Nutrition in Cancer Care

Dysphagia section in the Oral Complications of Chemotherapy and Head/Neck Radiation summary

Cellular Classification of Esophageal Cancer

Adenocarcinomas, typically arising in Barrett esophagus, account for at least 50% of malignant lesions, and the incidence of this histology appears to be rising. Barrett esophagus contains glandular epithelium cephalad to the esophagogastric junction.

Gastrointestinal stromal tumors can occur in the esophagus and are usually benign. (Refer to the PDQ summary on Gastrointestinal Stromal Tumors Treatment for more information.)

Stage Information for Esophageal Cancer

Note: The American Joint Committee on Cancer (AJCC) has published the 8th edition of the AJCC Cancer Staging Manual, which includes revisions to the staging for this disease. Implementation of the 8th edition began in January 2018. The PDQ Adult Treatment Editorial Board, which maintains this summary, is reviewing the revised staging and will make appropriate changes as needed.

One of the major difficulties in allocating and comparing treatment modalities for patients with esophageal cancer is the lack of precise preoperative staging. The stage determines whether the intent of the therapeutic approach will be curative or palliative.

Staging Evaluation

Standard noninvasive staging modalities include the following:

Endoscopic ultrasound.

Computed tomography (CT) scan of the chest and abdomen.

Positron emission tomography (PET)-CT scan.

The overall tumor depth staging accuracy of endoscopic ultrasound is 85% to 90%, compared with 50% to 80% for CT; the accuracy of regional nodal staging is 70% to 80% for endoscopic ultrasound and 50% to 70% for CT.[1,2]

Thoracoscopy and laparoscopy have been used in esophageal cancer staging at some surgical centers.[4,5,6] An intergroup trial reported an increase in positive lymph node detection to 56% of 107 evaluable patients with the use of thoracoscopy/laparoscopy, from 41% (with the use of noninvasive staging tests, e.g., CT, magnetic resonance imaging, and endoscopic ultrasound), with no major complications or deaths.[7]

Noninvasive PET scan using the radiolabeled glucose analog fluorine F 18-fludeoxyglucose (18F-FDG) for preoperative staging of esophageal cancer is more sensitive than a CT scan or endoscopic ultrasound in detection of distant metastases. A recent study of 262 patients with potentially resectable esophageal cancer demonstrated the utility of 18F-FDG-PET in identifying confirmed distant metastatic disease in at least 4.8% of patients after standard evaluation.[8,9,10,11,12]

AJCC Staging System

The AJCC has designated staging by TNM classification to define cancer of the esophagus and esophagogastric junction.[13] Tumors located in the gastric cardia within 5 cm of the gastroesophageal junction with extension into the esophagus or the gastroesophageal junction are classified as esophageal cancer. Tumors with the epicenter of the tumor located in the gastric cardia beyond 5 cm of the gastroesophageal junction or without extension into the esophagus are classified as gastric cancer.[13] (Refer to the Stage Information section in the PDQ summary on Gastric Cancer Treatment for more information.)

In contrast to earlier classification systems, the 2010 AJCC TNM staging system differentiates by histologic subtype, with an individualized staging system for squamous cell carcinoma versus adenocarcinoma, reflecting differences in biology.[13]

The classification of involved abdominal lymph nodes as M1 disease is controversial. The presence of positive abdominal lymph nodes does not appear to have a prognosis as grave as that for metastases to distant organs.[14] Patients with regional and/or celiac axis lymphadenopathy should not necessarily be considered to have unresectable disease caused by metastases. Complete resection of the primary tumor and appropriate lymphadenectomy is attempted when possible.

Stage IA squamous cell cancer of the esophagus. Cancer has formed in the mucosa or submucosa layer of the esophagus wall. The cancer cells are grade 1 or the grade is unknown. Grade 1 cancer cells look more like normal cells under a microscope and grow and spread more slowly than grade 2-3 cancer cells.

Stage IB squamous cell cancer of the esophagus. Cancer has formed in the mucosa or submucosa layer of the esophagus wall, and the cancer cells are grade 2-3; OR cancer has formed in the mucosa or submucosa layer and spread into the muscle layer or the connective tissue layer of the esophagus wall, and the cancer cells are grade 1. Grade 1 cancer cells look more like normal cells under a microscope and grow and spread more slowly than grade 2-3 cancer cells. The tumor is in the lower esophagus or it is not known where the tumor is.

Stage IIA squamous cell cancer of the esophagus (1). The tumor is in either the upper or middle esophagus. Cancer has spread into the muscle layer or the connective tissue layer of the esophagus wall. The cancer cells are grade 1. Grade 1 cancer cells look more like normal cells under a microscope and grow and spread more slowly than grade 2-3 cancer cells.Stage IIA squamous cell cancer of the esophagus (2). The tumor is in the lower esophagus or it is not known where the tumor is. Cancer has spread into the muscle layer or the connective tissue layer of the esophagus wall. The cancer cells are grade 2-3. Grade 2-3 cancer cells look more abnormal under a microscope and grow and spread more quickly than grade 1 cancer cells.

Stage IIB squamous cell cancer of the esophagus. The tumor is in either the upper or middle esophagus. Cancer has spread into the muscle layer or the connective tissue layer of the esophagus wall, and the cancer cells are grade 2-3; OR cancer is in the mucosa or submucosa layer and may have spread into the muscle layer of the esophagus wall, and cancer is found in 1 or 2 lymph nodes near the tumor. Grade 2-3 cancer cells look more abnormal under a microscope and grow and spread more quickly than grade 1 cancer cells.

Stage IIIA squamous cell cancer of the esophagus (1). Cancer is in the mucosa or submucosa layer and may have spread into the muscle layer of the esophagus wall, and cancer is found in 3 to 6 lymph nodes near the tumor; OR cancer has spread into the connective tissue layer of the esophagus wall, and cancer is found in 1 or 2 lymph nodes near the tumor.Stage IIIA squamous cell cancer of the esophagus (2). Cancer has spread into the (a) diaphragm, (b) pleura (tissue that covers the lungs and lines the inner wall of the chest cavity), or (c) membrane (sac) around the heart. The cancer can be removed by surgery.

Stage IIIC squamous cell cancer of the esophagus (1). Cancer has spread into the (a) diaphragm, (b) pleura (tissue that covers the lungs and lines the inner wall of the chest cavity), or (c) membrane (sac) around the heart. The cancer can be removed by surgery. Cancer is found in 1 to 6 lymph nodes near the tumor.Stage IIIC squamous cell cancer of the esophagus (2). Cancer has spread into nearby organs, such as the aorta, trachea, or spine, and the cancer cannot be removed by surgery; OR cancer has spread to 7 or more lymph nodes near the tumor.

a Location of the primary cancer site is defined by the position of the upper (proximal) edge of the tumor in the esophagus.

b(1) At least maximal dimension of the tumor must be recorded, and (2) multiple tumors require the T(m) suffix.

c Number must be recorded for total number of regional nodes sampled and total number of reported nodes with metastasis.

d High-grade dysplasia includes all noninvasive neoplastic epithelia that was formerly called carcinoma in situ, a diagnosis that is no longer used for columnar mucosae anywhere in the gastrointestinal tract.

IV

Any

Any

Any T, Any N, M1

TX = Primary tumor cannot be assessed.

Stage IV squamous cell cancer of the esophagus. The cancer has spread to other parts of the body, such as the lung, liver, adrenal gland, kidney, or bone.

Stage IA adenocarcinoma of the esophagus. Cancer has formed in the mucosa or submucosa layer of the esophagus wall. The cancer cells are grade 1 or 2. Grade 1 and 2 cancer cells look more like normal cells under a microscope and grow and spread more slowly than grade 3 cancer cells.

Stage IB adenocarcinoma of the esophagus. Cancer has formed in the mucosa or submucosa layer of the esophagus wall, and the cancer cells are grade 3. Grade 3 cancer cells look more abnormal under a microscope and grow and spread more quickly than grade 1 or 2 cancer cells; OR cancer has formed in the mucosa or submucosa layer and spread into the muscle layer of the esophagus wall, and the cancer cells are grade 1 or 2. Grade 1 and 2 cancer cells look more like normal cells under a microscope and grow and spread more slowly than grade 3 cancer cells.

Stage IIA adenocarcinoma of the esophagus. Cancer has spread into the muscle layer of the esophagus wall. The cancer cells are grade 3. Grade 3 cancer cells look more abnormal under a microscope and grow and spread more quickly than grade 1 or 2 cancer cells.

Stage IIB adenocarcinoma of the esophagus. Cancer has spread into the connective tissue layer of the esophagus wall; OR cancer is in the mucosa or submucosa layer and may have spread into the muscle layer of the esophagus wall, and cancer is found in 1 or 2 lymph nodes near the tumor.

Stage IIIA adenocarcinoma of the esophagus (1). Cancer is in the mucosa or submucosa layer and may have spread into the muscle layer of the esophagus wall, and cancer is found in 3 to 6 lymph nodes near the tumor; OR cancer has spread into the connective tissue layer of the esophagus wall, and cancer is found in 1 or 2 lymph nodes near the tumor.Stage IIIA adenocarcinoma of the esophagus (2). Cancer has spread into the (a) diaphragm, (b) pleura (tissue that covers the lungs and lines the inner wall of the chest cavity), or (c) membrane (sac) around the heart. The cancer can be removed by surgery.

Stage IIIC adenocarcinoma of the esophagus (1). Cancer has spread into the (a) diaphragm, (b) pleura (tissue that covers the lungs and lines the inner wall of the chest cavity), or (c) membrane (sac) around the heart. The cancer can be removed by surgery. Cancer is found in 1 to 6 lymph nodes near the tumor.Stage IIIC adenocarcinoma of the esophagus (2). Cancer has spread into nearby organs, such as the aorta, trachea, or spine, and the cancer cannot be removed by surgery; OR cancer has spread to 7 or more lymph nodes near the tumor.

a(1) At least maximal dimension of the tumor must be recorded, and (2) multiple tumors require the T(m) suffix.

b Number must be recorded for total number of regional nodes sampled and total number of reported nodes with metastasis.

c High-grade dysplasia includes all noninvasive neoplastic epithelia that was formerly called carcinomain situ, a diagnosis that is no longer used for columnar mucosae anywhere in the gastrointestinal tract.

IV

Any

Any T, Any N, M1

TX = Primary tumor cannot be assessed.

Stage IV adenocarcinoma of the esophagus. The cancer has spread to other parts of the body, such as the lung, liver, adrenal gland, kidney, or bone.

Treatment Option Overview for Esophageal Cancer

For patients with minimally invasive resectable esophageal cancer, surgical resection alone offers the potential for cure. In contrast, therapeutic management for patients with locally advanced resectable esophageal cancer has evolved significantly over the last few decades. Because of the risk of distant metastases and local relapse, multimodality therapy with integration of chemotherapy, radiation therapy, and surgical resection has become the standard of care.

Combined modality therapies are under clinical evaluation and include the following:

Surgery alone.

Chemotherapy.

Radiation therapy.

Effective palliation may be obtained in individual cases with various combinations of the following:

Chemoradiation followed by surgery (for patients with stage IVA disease)

Chemotherapy, which has provided partial responses for patients with metastatic distal esophageal adenocarcinomas

Nd:YAG endoluminal tumor destruction or electrocoagulation

Endoscopic-placed stents to provide palliation of dysphagia

Radiation therapy with or without intraluminal intubation and dilation

Intraluminal brachytherapy to provide palliation of dysphagia

Recurrent Esophageal Cancer

Palliative use of any of the standard therapies, including supportive care

Surgery

Surgery (Barrett esophagus)

The prevalence of Barrett metaplasia in adenocarcinoma of the esophagus suggests that Barrett esophagus is a premalignant condition. Endoscopic surveillance of patients with Barrett metaplasia may detect adenocarcinoma at an earlier stage that is more amenable to curative resection. Strong consideration should be given to resection in patients with high-grade dysplasia in the setting of Barrett metaplasia.[6]

Surgery (esophageal cancer)

The survival rate of patients with esophageal cancer is poor. Surgical treatment of resectable esophageal cancers results in 5-year survival rates of 5% to 30%, with higher survival rates in patients with early-stage cancers.[7] Asymptomatic small tumors confined to the esophageal mucosa or submucosa are detected only by chance. Surgery is the treatment of choice for these small tumors. Once symptoms are present (e.g., dysphagia, in most cases), esophageal cancers have usually invaded the muscularis propria or beyond and may have metastasized to lymph nodes or other organs.

In some patients with partial esophageal obstruction, dysphagia may be relieved by placement of an expandable metallic stent [8] or by radiation therapy if the patient has disseminated disease or is not a candidate for surgery. Alternative methods of relieving dysphagia have been reported, including laser therapy and electrocoagulation to destroy intraluminal tumor.[9,10,11]

In the presence of complete esophageal obstruction without clinical evidence of systemic metastasis, surgical excision of the tumor with mobilization of the stomach to replace the esophagus has been the traditional means of relieving the dysphagia.

The optimal surgical approach for radical resection of esophageal cancer is not known. One approach advocates transhiatal esophagectomy with anastomosis of the stomach to the cervical esophagus. A second approach advocates abdominal mobilization of the stomach and transthoracic excision of the esophagus with anastomosis of the stomach to the upper thoracic esophagus or the cervical esophagus. One study concluded that transhiatal esophagectomy was associated with lower morbidity than was transthoracic esophagectomy with extended en bloc lymphadenectomy; however, median overall disease-free and quality-adjusted survival did not differ significantly.[12] Similarly, no differences in long-term quality of life (QOL) using validated QOL instruments have been reported.[13] More recently, minimally invasive approaches that offer potential advantages of smaller incisions, decreased intraoperative blood loss, fewer postoperative complications, and shorter hospital stays have emerged. However, the ability to obtain negative surgical margins, the adequacy of lymph node dissection, and long-term outcomes have not been fully established with this approach.[14]

In the United States, the median age of patients who present with esophageal cancer is 67 years.[15] The results of a retrospective review of 505 consecutive patients who were operated on by a single surgical team over 17 years found no difference in the perioperative mortality, median survival, or palliative benefit of esophagectomy on dysphagia when the patients older than 70 years were compared with their younger peers.[16][Levels of evidence: 3iiA and 3iiB] All of the patients in this series were selected for surgery on the basis of potential operative risk. Age alone does not determine therapy for patients with potentially resectable disease.

Surgical treatment of esophageal cancer is associated with an operative mortality rate of less than 10%.[7] In an attempt to avoid perioperative mortality and to relieve dysphagia, definitive radiation therapy in combination with chemotherapy has been studied.

Preoperative Chemoradiation Therapy

On the basis of several randomized trial results, chemoradiation followed by surgery is a standard treatment option for patients with stages IB, II, III, and IVA esophageal cancer.

Phase III trials have compared preoperative concurrent chemoradiation therapy with surgery alone for patients with esophageal cancer.[17,18,19,20,21,21,22,23][Level of evidence: 1iiA] The benefit of neoadjuvant chemoradiation has been controversial because of contradictory results of early randomized studies.[17,18,19,20] However, the Chemoradiotherapy for Oesophageal Cancer Followed by Surgery Study (CROSS) has definitively demonstrated a survival benefit for preoperative chemoradiation compared with surgery alone in locally advanced esophageal cancer.[21]

For early-stage tumors, the role of preoperative chemoradiation remains controversial. Although the CROSS study included early-stage patients, the Francophone de Cance´rologie Digestive (FFCD) 9901 study (NCT00047112)[23], which included only early-stage (stage I or II) patients, failed to demonstrate a survival advantage in this group of patients.

Evidence (preoperative chemoradiation therapy):

The CROSS study randomly assigned 366 patients with resectable esophageal or junctional cancers to receive either surgery alone or weekly administration of carboplatin (dose titrated to achieve an AUC [area under the curve] of 2 mg/mL/minute) and paclitaxel (50 mg/m2 of BSA [body surface area]) and concurrent radiation therapy (41.4 Gy in 23 fractions) administered over 5 weeks. Most patients enrolled in the CROSS trial (75%) had adenocarcinoma.[21,24][Level of evidence: 1iiA]

A complete pathologic response was achieved in 29% of patients who underwent resection after chemoradiation therapy. A pathologic complete response was observed in 23% of patients with adenocarcinoma compared with 49% of patients with squamous cell carcinoma (P = .008).

Postoperative complications and in-hospital mortality were equivalent in both groups. The most common hematologic side effects in the chemoradiation group were leukopenia (6%) and neutropenia (2%). The most common nonhematologic side effects were anorexia (5%) and fatigue (3%).

With a median follow-up of 84 months, the 5-year progression-free survival (PFS) was 44% in the preoperative chemoradiation group compared with 27% in the surgery-alone group (HR, 0.61 [0.47–0.78]). Preoperative chemoradiation therapy reduced locoregional recurrence from 34% to 14% (P < .001) and peritoneal carcinomatosis from 14% to 4% (P < .001). There was a small but significant effect on hematogenous dissemination in favor of the chemoradiation therapy group (35% vs. 29%; P = .025).[22,24][Level of evidence: 1iiDii]

At a median follow-up of more than 8 years, there was no significant difference between the surgery alone and combined modality therapy with respect to median survival (17.6 months vs. 16.9 months), OS (16% vs. 30% at 3 years), or disease-free survival (16% vs. 28% at 3 years).

An intergroup trial (CALGB-9781 [NCT00003118]) planned to randomly assign 475 patients with resectable squamous cell or adenocarcinoma of the thoracic esophagus to treatment with preoperative chemoradiation therapy (5-FU, cisplatin, and 50.4 Gy) followed by esophagectomy and nodal dissection or surgery alone. The trial was closed as a result of poor patient accrual; however, results from the 56 enrolled patients, with a median follow-up of 6 years, were reported.[20][Level of evidence: 1iiA]

To further evaluate the impact of neoadjuvant chemoradiation therapy for early-stage disease, FFCD 9901 randomly assigned 195 patients with stage I or stage II esophageal cancer to receive surgery alone or neoadjuvant chemoradiation therapy (45 Gy in 25 fractions administered with two courses of 5-FU [800 mg/m2] and cisplatin [75 mg/m2]) followed by surgery.[23][Level of evidence: 1iiA]

At interim analysis, accrual to the study was stopped early because of futility.

With a median follow-up of 94 months, there was no significant improvement in 3-year OS with chemoradiation (48% vs. 53%, P = .94); there was a significantly higher postoperative mortality rate of 11.1% versus 3.4% (P = .049).

Preoperative Chemotherapy

The effects of preoperative chemotherapy are being evaluated in randomized trials. Several studies have demonstrated a survival benefit with preoperative chemotherapy compared with surgery alone.[25,26,27] However, one large randomized study failed to confirm a survival benefit with preoperative chemotherapy.[28] Compared with preoperative chemotherapy alone, preoperative chemoradiation therapy improves pathologic response and may improve outcomes.[29]

Evidence (preoperative chemotherapy):

An intergroup trial (NCT00525785) randomly assigned 440 patients with local and operable esophageal cancer of any cell type to three cycles of preoperative 5-FU and cisplatin followed by surgery and two additional cycles of chemotherapy versus surgery alone.[28][Level of evidence: 1iiA]

After a median follow-up of 55 months, there were no significant differences in median survival between the chemotherapy-plus-surgery group (14.9 months) and the surgery-alone group (16.1 months); median survival at 2 years was 35% for the chemotherapy-plus-surgery group and 37% for the surgery-alone group.

The addition of chemotherapy did not increase the morbidity associated with surgery.

The Medical Research Council Oesophageal Cancer Working Party randomly assigned 802 patients with resectable esophageal cancer, also of any cell type, to two cycles of preoperative 5-FU and cisplatin followed by surgery versus surgery alone.[25][Level of evidence: 1iiA]

The interpretation of the results from the intergroup and preoperative chemotherapy trials is challenging because T or N staging was not reported, and prerandomization and radiation could be offered at the discretion of the treating oncologist.

The Japanese Clinical Oncology Group randomly assigned 330 patients with clinical stage II or III, excluding T4, squamous cell carcinomas to receive either two cycles of preoperative cisplatin and 5-FU followed by surgery or surgery followed by postoperative chemotherapy of the same regimen. A planned interim analysis was conducted after patient accrual; although the primary endpoint of PFS was not met, there was a significant benefit in OS among patients treated with preoperative chemotherapy (P = .01). As a result of these findings, the Data and Safety Monitoring Committee recommended early closure of the study.[26][Level of evidence: 1iiC]

With a median follow-up of 61 months, the 5-year OS was 55% among patients treated with preoperative chemotherapy compared with 43% among patients treated with postoperative chemotherapy (P = .04). However, there was no significant difference between groups with respect to PFS (5-year PFS, 39% vs. 44%; P = .22).

Additionally, there were no significant differences between the two groups with respect to postoperative complications or treatment-related toxicities.

The Fédération Nationale des Centres de Lutte contre le Cancer and the FFCD randomly assigned 224 patients with resectable adenocarcinoma of the lower esophagus, gastroesophageal junction, or stomach to receive either perioperative chemotherapy and surgery (n = 113) or surgery alone (n = 111). Chemotherapy consisted of two or three preoperative cycles of intravenous (IV) cisplatin (100 mg/m2) on day 1 and continuous IV infusion of 5-FU (800 mg/m2) for 5 consecutive days (day 1–5) every 28 days, and three or four postoperative cycles of the same regimen.[27][Level of evidence: 1iiA]

Grade 3 and 4 toxicity occurred in 38% of patients treated with perioperative chemotherapy, but there was no increase in postoperative morbidity.

The Preoperative Chemotherapy or Radiochemotherapy in Esophago-gastric Adenocarcinoma Trial (POET) sought to evaluate the additional benefit of radiation therapy to preoperative chemotherapy. Patients were randomly assigned to receive either induction chemotherapy (15 weeks) followed by surgery or chemotherapy (12 weeks) followed by chemoradiation therapy (3 weeks) followed by surgery.[29][Level of evidence: 1iiA]

The study was closed early because of poor accrual. In total, 126 patients were randomly assigned.

For patients who are deemed either medically inoperable or have tumors that are unresectable, the efficacy of definitive chemoradiation has been established in numerous randomized controlled trials.[30,31] For patients with squamous cell carcinomas of the esophagus, definitive chemoradiation may offer equivalent outcomes compared with preoperative chemoradiation followed by surgical resection.[32,33]

There was an improvement in 5-year survival for the combined modality group (27% vs. 0%).

An 8-year follow-up of this trial demonstrated an OS rate of 22% for patients receiving chemoradiation therapy.

Intergroup-0123 (RTOG-9405 [NCT00002631]) was conducted in an attempt to improve upon the results of RTOG-8501. Intergroup-0123 randomly assigned 236 patients with localized esophageal tumors to undergo chemoradiation with high-dose radiation therapy (64.8 Gy) and four monthly cycles of 5-FU and cisplatin versus conventional-dose radiation therapy (50.4 Gy) and the same chemotherapy schedule.[31][Level of evidence: 1iiA]

Although originally designed to accrue 298 patients, this trial was closed in 1999 after a planned interim analysis showed that it was statistically unlikely that there would be any advantage to using high-dose radiation.

This trial showed that chemotherapy plus radiation therapy provided a better 2-year survival rate than did radiation therapy alone, similar to results from the intergroup trial.

The PRODIGE5/ACCORD17 (NCT00861094) trial sought to evaluate and compare the efficacy and safety of oxaliplatin, fluorouracil, and leucovorin calcium (FOLFOX) versus 5-FU and cisplatin as the chemotherapy backbone among patients treated with definitive chemoradiation for localized esophageal cancer. In this multicenter, randomized, phase II and III trial, 267 patients were randomly assigned to receive either six cycles of FOLFOX (three cycles concomitant with radiation therapy), oxaliplatin (85 mg/m2), leucovorin (200 mg/m2), bolus 5-FU (400 mg/m2) and infusion 5-FU (1,600 mg/m2 over 46 hours) or four cycles of 5-FU (1,000 mg/m2 for 4 days) and cisplatin (75 mg/m2 on day 1). All patients received radiation therapy (50 Gy in 25 fractions).[35][Level of evidence: 1iiDiii]

With a median follow-up of 25.3 months, there was no significant difference in PFS (9.7 months with FOLFOX vs. 9.4 months with 5-FU and cisplatin; P = .64).

There was one death caused by toxicity in the FOLFOX group versus six deaths in the 5-FU and cisplatin arm (P = .066).

There were no significant differences in grade 3 or 4 adverse events between treatment groups. Among toxicities of all grades, paresthesia, sensory neuropathy, and increases in aspartate transaminase and alanine transaminase were more common in the FOLFOX group; whereas, increases in serum creatinine, mucositis, and alopecia were more common in the 5-FU and cisplatin group.

A phase III German trial also compared induction chemotherapy (three courses of bolus 5-FU, leucovorin, etoposide, and cisplatin) followed by chemoradiation therapy (cisplatin, etoposide, and 40 Gy) followed by surgery (arm A), or the same induction chemotherapy followed by chemoradiation therapy (at least 65 Gy) without surgery (arm B) for patients with T3 or T4 squamous cell carcinoma of the esophagus. OS was the primary outcome.[32][Level of evidence: 1iiA]

The 3-month mortality rate was 9.3% in the surgery arm compared with 0.8% in the chemoradiation arm (P = .002).

Postoperative Radiation Therapy

Two randomized trials have shown no significant OS benefit for postoperative radiation therapy compared with surgery alone.[36,37][Level of evidence: 1iiA] All newly diagnosed patients should be considered candidates for therapies and clinical trials comparing various treatment modalities. Information about ongoing clinical trials is available from the NCI website.

Stage 0 Esophageal Cancer Treatment

Standard Treatment Options for Stage 0 Esophageal Cancer

Stage 0 squamous cell esophageal cancer is rarely seen in the United States, but surgery has been used.[1,2] For early-stage minimally invasive esophageal cancer, surgical and endoscopic techniques offer high rates of cure.[3,4]

Surgery.

Endoscopic resection.

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

Stage I Esophageal Cancer Treatment

Standard treatment options for stage I esophageal cancer include the following:[1,2,3,4,5]

Chemoradiation followed by surgery.

Surgery alone.

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

Esophageal cancer responds to many anticancer agents. Objective response rates of 30% to 60% and median survivals of less than 1 year are commonly reported with platinum-based combination regimens with 5-fluorouracil, taxanes, topoisomerase inhibitors, hydroxyurea, or vinorelbine.[1,4,9] Trastuzumab may be effective in combination with chemotherapy among patients with tumors that overexpress HER2-neu.[10][Level of evidence: 1iiA]

Clinical trials evaluating single-agent or combination chemotherapy.

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

Recurrent Esophageal Cancer Treatment

Palliation presents difficult problems for all patients with recurrent esophageal cancer. All patients should be considered candidates for clinical trials as outlined in the Treatment Option Overview section of this summary.

Standard treatment options:

Palliative use of any of the standard therapies, including supportive care.

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

Changes to This Summary (02 / 06 / 2018)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

General Information About Esophageal Cancer

Updated statistics with estimated new cases and deaths for 2018 (cited American Cancer Society as reference 1).

Stage Information for Esophageal Cancer

Editorial changes were made to this section.

This summary is written and maintained by the PDQ Adult Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.

About This PDQ Summary

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about treatment of esophageal cancer. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

Reviewers and Updates

This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

Board members review recently published articles each month to determine whether an article should:

be discussed at a meeting,

be cited with text, or

replace or update an existing article that is already cited.

Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.

The lead reviewer for Esophageal Cancer Treatment is:

Jennifer Wo, MD (Massachusetts General Hospital)

Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.

Levels of Evidence

Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

Permission to Use This Summary

PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as "NCI's PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary]."

Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in Visuals Online, a collection of over 2,000 scientific images.

Disclaimer

Based on the strength of the available evidence, treatment options may be described as either "standard" or "under clinical evaluation." These classifications should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Managing Cancer Care page.

Contact Us

More information about contacting us or receiving help with the Cancer.gov website can be found on our Contact Us for Help page. Questions can also be submitted to Cancer.gov through the website's Email Us.

This information does not replace the advice of a doctor. Healthwise, Incorporated disclaims any warranty or liability for your use of this information. Your use of this information means that you agree to the Terms of Use and Privacy Policy. Learn how we develop our content.

Healthwise, Healthwise for every health decision, and the Healthwise logo are trademarks of Healthwise, Incorporated.

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